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Role of Histone Methyltransferase in Breast Cancer
Published in Meenu Gupta, Rachna Jain, Arun Solanki, Fadi Al-Turjman, Cancer Prediction for Industrial IoT 4.0: A Machine Learning Perspective, 2021
Surekha Manhas, Zaved Ahmed Khan
The associated G9a-based proteins, including GLP and EHMT1, whose gene locations are not found in the HLA/MHC locus, are able to form heterodimer in vivo along with G9a that is critically needed for H3K9me2-based methylation activity [92]. Any kind of genetic deletion associated with both of these proteins leads to a significant H3K9me2 reduction, representing that both protein subunits are very essential to enzyme-based activities [93]. Mutation at the active sites of the gene has shown to be found in in-vivo studies that indicated that HMNT activity plays an important role in H3K9me2 methylation [94]. However, global neuron analysis of gene expression in mice, along with specifically targeted deletions in the case of either GLP or G9a, identified the observable difference that might be created due to the differential subunit requirement in gene expression [95]. Furthermore, GLP loss is related to Kleefstra syndrome. This genetic disorder, found very rarely, is characterized by impairments in physical/social activities and intellectual disability [96]. No analysis has been done on the functional role of immune defense cells in this syndrome. Since GLP might display a specific potent role in gene regulation, it might be tested directly.
C syndrome - what do we know and what could the future hold?
Published in Expert Opinion on Orphan Drugs, 2019
Roser Urreizti, Daniel Grinberg, Susanna Balcells
The relatively broad clinical spectrum of OCS overlaps other clinical entities and some patients initially considered as OCS have been finally re-diagnosed to other syndromes such as the Kleefstra Syndrome mentioned previously, Varady Syndrome or Kabuki syndrome [21,27,39–41]. In 1999, a new syndrome highly overlapping OCS but with a more severe outcome was delineated. This C-like syndrome or Bohring-Opitz Syndrome (BOS, MIM # 605,039) is clinically -and genetically- more homogeneous and it is mainly characterized by trigonocephaly (and microcephaly), nevus simplex (flammeus), intrauterine growth retardation (IUGR), failure to thrive, severe to profound developmental delay and characteristic fixed flexions of the elbows, wrists and metacarpophalangeal joints, known as BOS posture [42]. BOS is mainly due to mutations in the ASXL1 gene [42–44]. In near one third of the patients fitting a typical clinical BOS phenotype no mutations in ASXL1 can be detected, suggesting that it is a heterogeneous entity. In this sense, mutations in ASXL3 [45]; ASXL2 [46] and KLHL7 [47] have been identified in patients clinically overlapping BOS.
Conditioned courtship suppression in Drosophila melanogaster
Published in Journal of Neurogenetics, 2021
Nicholas Raun, Spencer Jones, Jamie M. Kramer
With the increased capacity for DNA sequencing over the past decade, identification of human disease genes has progressed at an incredible rate. For example, there are now over 1300 genes known to be involved in intellectual disability (Kochinke et al., 2016), a neurodevelopmental disorder characterized by limitations in intellectual ability and adaptive behaviours. The unbiased identification of candidate disease genes for neurodevelopmental disorders (NDDs) is no longer a bottle neck. Instead, the focus has shifted to better understanding gene function. Drosophila is a beneficial model to study the neuronal function of NDD genes, as around three-quarters of all human intellectual disability genes are conserved in flies (Vissers, Gilissen, & Veltman, 2016). Courtship conditioning is a robust and relatively easy assay requiring very little specialized equipment. Furthermore, as it manipulates an ethologically relevant behaviour, it may offer a benefit over traditional associative memory assays, which present scenarios that an animal would never encounter in nature (König et al., 2017). As such, several studies have used cVA-retrievable courtship memory as a functional assay to assess the relevance of orthologs to genes involved in rare neurodevelopmental disorders. For example, Kleefstra syndrome is a disorder characterized by intellectual disability and autism, and is caused by mutations in the EHMT1 gene (Kleefstra et al., 2005), encoding a histone methyl transferase. The Drosophila EHMT1 ortholog, G9a, was shown to be required in the adult MB for cVA-retrievable courtship memory (Kramer et al., 2011). In a search for additional genes underlying Kleefstra syndrome, mutations were identified in the KMT2C gene, encoding another histone methyltransferase with no known functional link to EHMT1 (Koemans, Kleefstra, et al., 2017). In flies, a functional link was suggested between G9a and the KMT2C ortholog, trr, through genetic interactions studies in the developing wing (Kleefstra et al., 2012). Like G9a, trr is also required in the MB for cVA-dependent courtship memory without effecting MB development. Interestingly, gene expression defects were highly overlapping in brains that were depleted for G9a and trr. The phenotypic convergence in flies, along with the overlapping clinical phenotype provided functional justification for the classification of mutations in these two genes as causal factors underlying Kleefstra syndrome (MIM 617768 and 610253) (Kleefstra et al., 2012; Koemans, Kleefstra, et al., 2017).